This application will bring forward novel topical microbicide products that will be formulated using pH and thermo sensitive gels and intravaginal rings. To ensure that these products in their formulations are safe and effective, the Explant Core will evaluate them for toxicity to cervcial explant tissues and efficacy against HIV- 1 infection. Over years 1 through 3, 10 gels and 10 ring formulations (20 total) will be evaluated yearly. Four combination products (e.g. two product candidates in gels or one product in a gel and one product in a ring) will be evaluated in year 2 and 3. The unique aspects of this Core will be studying the timing issues of product application and whether the proudct(s) is effective if used several hours prior to HIV-1 exposure to test for coital independance. The products that are the least toxic and most effective will be further refined for development. Over years 4 and 5, this refined evaluation will include use of product in the cervical explant cultures in the presence of seminal plasma. Because seminal plasma will influence the infectivity of HIV-1, it is necessary to include these studies. To ensure that the products that are being developed are safe, the Explant Core in conjunction with the Virology Core will evaluate cervicovaginal lavages obtained from women using the placebo formulations of gels to measure innate immune factors and intrinsic anti-microbial activity. The work provided by this Core will serve Projects 1 (Novel Delivery Systems) and 2 (Microbicide Performance Analysis). The findings from this Core will be used by Project 3 to ensure only those products are the safest are used in women. Collectively, this Core will evaluate new product formulations for safety and efficacy against HIV-1 using a state-of-the-art cervical explant culture system. The findings from this Core will help to quickly evaluate new products to move the microbicide product pipeline forward. Relevance: Microbicides are being developed to prevent the spread of HIV-1. The Explant Core will provide the investigators of this application information regarding microbicide safety and the ability to protect against HIV-1 infection using human tissue that would normally be discarded after surgery. The human tissue used by these scientists provide us the best bridge between the laboratory and the clinic to study microbicides.